EU/3/06/394

Orphan designation

On 28 August 2006, orphan designation (EU/3/06/394) was granted by the European Commission to Analytica International GmbH, Germany, for autologous tumor-derived immunoglobulin idiotype coupled to keyhole limpet haemocyanin for the treatment of follicular lymphoma.

The sponsorship was transferred to Analytica International Inc. - Outcomes Research and Pricing, Germany, in May 2011 and subsequently to Biovest Europe Limited, United Kingdom, in September 2011.

Follicular lymphoma is a type of cancer of the lymphatic system. The lymphatic system is part of the body’s immune system and helps fighting infections. It is a complex system made up of organs such as the bone marrow, the thymus (a gland behind the breast bone), the spleen (an organ in the abdomen, near the stomach), and the lymph nodes (or lymph glands, located throughout the body), which are connected by a network of tiny lymphatic vessels. There are two main types of cells, which make up the lymphatic tissue. These cells are called lymphocytes and belong to the group of white blood cells. The two types are called B lymphocytes (B cells) and T lymphocytes (T cells). There are several different types of lymphomas. In follicular lymphoma, the cancer cells are related to the B-lymphocytes. Follicular lymphoma is a life-threatening disease.

At the time of designation follicular lymphoma affected approximately 2.2 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 101,000 people, and is below the threshold for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and knowledge of the Committee for Orphan Medicinal Products (COMP).

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union (EU 27), Norway, Iceland and Liechtenstein. This represents a population of 459,700,000 (Eurostat 2004).

At the time of submission of the application for orphan drug designation, several medicinal products were authorised in the European Union for use in follicular lymphoma. The choice of treatment depends in particular on the extension of the disease as well as on the responses to therapies previously prescribed.

Autologous tumor-derived immunoglobulin idiotype coupled to keyhole limpet haemocyanin might be of potential significant benefit for the treatment of follicular lymphoma because it may act in a different way from other available medicines and it might improve the long-term outcome of the patients. The assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

The medicinal product is a vaccine that contains proteins originating from the cancer cells of the patient him/herself and the copper-containing respiratory protein, keyhole limpet haemocyanin, from the gastropod (mollusc) Megathura crenulata. According to the sponsor, a specific protein from the surface of the cancer cells is isolated and manipulated in the laboratory to be further injected back into the patient. It is expected that following the injection of this “patient-specific vaccine”, the body’s defence system (immune system) will recognise this cancer cell protein as a foreign body and will react against it by producing specific antibodies. It is expected that after vaccination, the immune system will not only recognise the vaccine as foreign, but also the cancer cells that carry the same surface protein as that used to prepare the patient-specific vaccine. The patient body’s immune system could then kill these cancer cells.

The evaluation of the effects of autologous tumor-derived immunoglobulin idiotype coupled to keyhole limpet haemocyanin in experimental models is ongoing.

At the time of submission of the application for orphan designation, clinical trials in patients with follicular lymphoma were ongoing.

Autologous tumor-derived immunoglobulin idiotype coupled to keyhole limpet haemocyanin was not authorised anywhere worldwide for treatment of follicular lymphoma or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 July 2006 recommending the granting of this designation.

the existence of alternative methods of diagnosis, prevention or treatment;

either the rarity of the condition (affecting not more than 5 in 10,000 people in the Community) or insufficient returns on investment.

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.